In my current game, my players are racing to keep Chernabog from rising. A powerful hellspawn might be quite fitting for Buffy. I kind of also like the idea of body snatchers for a one-shot. Especially if you infect a player and inject some paranoia into the group.

If you've ever seen Outlaw Star, while playing Shadowrun several years ago, I presented the episode with the psychic cactus alien... thankfully only one of the players had seen it and he didn't spoil it for everyone else.

It's a big world, and it never stays the same. OMG I LOOOVES TO CHANGE MY SIGNATURE!!!!
squeaky: you can take my base, but you can never take my pie

I went with an entlike creature that tapped its roots into baristas to mind-control them and set off natural disasters to build up a world tree that would restore the life of the city (while choking out its human denizens). So in many ways it was like a cultist for an Elder God. It got defeated when one of the characters dumped two entire containers of herbicide on it after going - just in time - to the coffee shop where it was about to kidnap its final victim.